Blood to be analyzed for diagnostic and monitoring purposes is customarily collected by venipuncture through a cannula or needle attached to an evacuated glass collection tube. Tubes are labelled and transported to the laboratory where they are identified, recorded and prepared for analysis. Separation of the serum or plasma phases from the blood cells is often necessary for laboratory analysis and is usually carried out by centrifugation. Once separated the phases are best kept in an inert container, physically and chemically isolated, to avoid disturbance of analyte concentrations. Some analytes may have specific requirements such as constant or low temperature, or shielding from light. The blood may contain infectious agents and should be kept isolated, preferably in a closed system to reduce exposure to laboratory personnel. Serum and plasma are commonly used analytical samples. If serum is desired the specimen must be permitted to clot or coagulate before further separation is attempted. If plasma is desired the specimen must have an anticoagulant mixed with it immediately after collection. For this purpose anticoagulant materials are commonly placed in blood collection devices at the time of manufacture.
Specimens which have been centrifuged are often subsequently aliquotted. Aliquotting is the process of dividing up samples for distribution among analyzer sites. This involves the transfer of analyte from the collection tube to one or more secondary containers. These secondary containers may be standard test tubes or custom sample cups for specific analyzers. To make the blood processing procedure efficient and safe collection tubes must offer containment, additives, identification and ease of handling.
The popular pre-evacuated blood collection tube (such as described by Kleiner U.S. Pat. No. 2,460,641) has the following advantages: once sterilized, its interior remains sterile without additional packaging; simplicity of structure and use, in that its basic form consists of only a glass tube permanently closed at one end with a rubber stopper in the open end; and it is self-healing when blood drawing is complete and the cannula which was used to puncture the rubber stopper has been removed. Such collection tubes are typically made of glass and are thus susceptible to breakage. Collection tube breakage is a very dangerous event because it may scatter sharp pieces of blood contaminated glass that may contain infectious agents such as the viruses associated with Acquired Immune Deficiency Syndrome or Hepatitis. A common mode of infection of laboratory and hospital staff is skin laceration by needles or broken glass.
One method of reducing the hazards associated with breakage is to coat the glass with plastic. Glass bottles coated with plastic are sold by the tradenames "Safemor" by Mallinckrodt Inc., "Safe-Cote" by Fisher Scientific Company of Pittsburgh, Pa, and "Second Skin" by Wheaton Safety Container Company of Mays Landing, NJ. Also found are plastic coated incandescent light bulbs, so coated to reduce hazards associated with explosion of the bulb. Plastic-coated glass exhibits increased strength over regular uncoated glass, thus reducing breakage. If the glass does break, the plastic contains both the glass fragments and the liquid within. However, these containers cannot be used to collect or process a sample of blood and are not intended for such use.
An alternative to coating a glass tube with plastic is to construct the whole tube from plastic. Unfortunately, while plastics have high breakage resistance few are capable of holding a vacuum over long periods of time (most manufacturers specify a 2 year shelf life for their evacuated glass tubes, and the International Standards Organization specifies that the volume of water drawn by an evacuated tube shall not deviate more than 10% before the tube's expiry date). Sarstedt Inc. produces a plastic tube, the "Monovette", but because of its poor vacuum retention it is used like a syringe and is not considered a convenient means of routine blood collection. Tzafon markets a plastic, evacuated blood collection tube under the tradename "Vacuette", but it cannot hold a vacuum over a prolonged period of time without external overpacking which must be removed prior to tube use. One object of this invention is to combine the properties of shatter resistance and vacuum retention in a single plastic tube which is easy to manufacture and use.
While breakage is a relatively infrequent event aliquotting is a routine procedure with similar associated hazards. Presently there are a number of aliquotting methods. A common method is to remove the stopper and use a dropper pipette to transfer some of the sample from the open primary tube to a secondary container. This procedure is hazardous: removal of the stopper generates infectious aerosols, and an open sample tube may easily be spilled. Another common method of aliquotting is to simply decant from the opened primary tube into secondary containers. This is even more hazardous because skill is required to decant a small amount of serum or plasma without spillage.
Some devices have been made which attempt to address these hazards. One such device is made by Helena Laboratories of Beaumont, Texas and sold by the tradename "Tip-Top" Dispenser Cap. The Tip Top dispenser is fastened to the open end of a centrifuged blood collection tube, inverted and squeezed to dispense a sample through an orifice to a sample cup. The major difficulty with the Tip Top dispenser and others like it is that it requires the hazardous step of stopper removal from the blood collection tube. A device which does not require stopper removal is made by Clean Tech SCI AG of Langenthal Switzerland and sold by the tradename "The CleanTech System". The CleanTech system consists of several components including a cannula to puncture the stopper, a machine to insert the cannula into the stopper, a pipette to access the sample through the stopper and a pump which fastens to the pipette to draw the sample from the tube. This device addresses many of the hazards of dispensing a sample but it is relatively complex, expensive and requires several steps to use. Another objective of this invention is to fill the need for an apparatus which allows blood to be contained and dispensed without risk of contamination or spillage through removal or handling of the stopper.
The work volume, both in number of blood specimens and number of tests (hence, aliquots) performed by typical clinical laboratories is rapidly increasing. This has greatly increased the likelihood of sample missidentification. Missidentified samples compromise patient care. Most blood collection tubes have paper labels affixed to their sides where the sample identification data can be handwritten. Identification in this manner is a time consuming and awkward task as it is difficult to write on a small, curved surface. The markings may get rubbed off through handling or obscured by foreign matter. In addition, mistakes can be made due to faulty transcription or illegible handwriting.
One alternative is to use pressure-sensitive labels. These labels change color in response to localized pressure. The markings are thus a part of the label and cannot be rubbed off. Such labels still suffer from the drawbacks of awkwardness, time consumption and human error.
Another alternative is to use barcodes, magnetic strips, or some other type of machine-readable label. These labels can be scanned by machine more quickly and with greater accuracy than a human can read handwriting. Such labels are relatively resistant to stains and abrasion and are unlikely to be misread if damaged. The main drawbacks are that such labels cannot be produced manually on site nor can they be easily read and interpreted by humans. A further objective of this invention is to provide sample identification which is simple, accurate, durable and both machine and human readable.
A blood specimen must be clotted to yield serum. Activation of the formation of this clot results as a consequence of contact with the glass collection tube in which the blood was collected and can be enhanced by the addition of various clot-activating materials as described in U.S. Pat. No. 4,189,382 by Zine. The National Committee for Clinical Laboratory Standards (NCCLS) recommends a waiting time of 20 to 30 minutes for clot formation to occur with no additives. If thrombin or silica particles are used as clotting activators, the NCCLS recommends 5 minute or 15 minute waiting times, respectively. The clotting process is much slower in conventional plastic tubes due to the difference in surface characteristics between glass and plastic. It is therefore necessary to add clot activators to initiate clotting in a plastic tube thus increasing the cost of the tube. Another objective of this invention is to provide a tube with integral clot activation such that the clotting process is initiated and enhanced without the addition of a clotting additive.
With the advent of high speed biochemical and chemical analyzers, the bulk of time and effort spent in a typical clinical laboratory in processing blood samples has shifted to the collection and preparation stages. Further gains in processing efficiency will be obtained by improving the handling characteristics of blood collection tubes.
One of the main obstacles to efficient specimen handling is the use of multiple blood collection tube sizes. The smaller tubes, often used to collect blood from children, are difficult to handle and have very little space on which to record sample identification information. The variation in tube size leads to nonuniform packaging and requirements for different sized test-tube racks. In modern blood analyzers there is a design trend towards systems which sample directly from blood collection tubes (primary tube sampling). The Hitachi-737 analyzer is one of the first of this type. Hence it is necessary to adapt the analyzer to whatever tube size is used to contain the specimen. Since most laboratories receive mixed batches of varying tube sizes, the analyzers must either be adjusted manually at great labor cost or automatically at great equipment cost.
Concurrent with the trend towards primary tube sampling is a trend towards automated sample handling. Procedures for blood separation and analysis expose laboratory personnel to infectious agents that may be passed through contact with blood; e.g. hepatitis or acquired immune deficiency syndrome. In addition, conventional batch processing of blood specimens is labor-intensive and has not generally been automated whereas other processes in clinical laboratories have. Automation of blood separation can effectively isolate laboratory personnel from the dangers of blood processing while theoretically increasing the speed of the overall analytical procedure.
A highly automated system would incorporate a robotic manipulator, automatic identification, and primary tube sampling analyzers. Automatic identification may require the tube to be manipulated in a very specific orientation, while some analyzers may require the exertion of a large insertion force along the tube's axis to seat it in the sampling bay. Present blood collection tubes are suboptimal for automatic manipulation because they have smooth, uniform outer surfaces. This makes it difficult for a robot to grip tubes firmly and repeatably with correct orientation.
A syringe has two of the characteristics needed for efficient sample handling. First, it has a single external size, regardless of the volume of blood drawn. Second, it has flanges on its exterior which could accommodate robotic gripping and orientation. Syringes are relatively inconvenient to use compared with evacuated collection tubes. This problem is addressed by Sarstedt's Monovette, which is a syringe-like collection tube with a plunger handle which can be removed after the blood is drawn and afterwards handled like a tube. This device, however, is less amenable to handling with an automated device than an evacuated collection tube. A further objective of this invention is to provide tubes which are more amenable to both human and automatic handling.
Co-pending U.S. application Ser. No. 07/033,769 by McEwen et al describes a method of separating a sample of blood contained in a tubular chamber wherein the tubular chamber and its contents are rotated about the chamber's longitudinal axis and providing a means of processing a sample of blood having the features of: ability to separate the blood phases under conditions which limit personnel exposure; maintenance of these phases separated and unchanged; monitoring of gross characteristics of the phases; ready adaptability to varying blood collection requirements; and flexibility for stand-alone use or integration into automated systems. The present invention provides an improved blood collection and separation device and provides an apparatus to dispense a portion of the separated blood sample separated in the blood collection and separation device according to the invention of McEwen et al as described in co-pending U.S. patent applications Ser. No. 07/033,769 and serial number 07/192,847. U.S. patent applications Ser. No. 07/033,769 and 07/192,847 are herein incorporated by reference.